Cation-dependent fusogenicity of an N-acyl phosphatidylethanolamine.
N-acyl phosphatidylethanolamines (NAPEs) are natural lipid components of many organisms. N-acylation of unsaturated phosphatidylethanolamines with a saturated fatty acid converts them from non-lamellar organizing lipids into lamellar organizing, acidic lipids which can interact with cations and potentially return to non-lamellar structures. These special properties make NAPEs candidates for fusogens. We tested the fusogenicity of one of the NAPEs, N-dodecanoyl-di-oleoylphosphatidylethanolamine (N-C12-DOPE) mixed with dioleoylphosphatidylcholine (DOPC) in liposomes. Binding and fusion to erythrocyte ghosts in the presence of 3 mM Ca2+ required at least 60 mol% of N-C12-DOPE. Fusion was not observed when phosphatidylglycerol or phosphatidylserine was substituted for N-C12-DOPE, indicating specificity for properties of this lipid. Binding of N-C12-DOPE/DOPC (70:30) liposomes required 1 mM Ca2+ while 1.25 mM Ca2+ and Mg2+ were sufficient for lipid mixing and delivery of encapsulated dextrans to erythrocyte ghosts. These liposomes also bound and possibly mixed lipid with nucleated U-937 cells in a Ca2+ -and endocytosis-dependent manner. Low pH-dependent fusion with ghosts was observed in the absence of any divalent cation, indicating that fusion with U-937 cells could result after endocytosis into the acidic endosomes. The possible mechanisms for N-C12-DOPE mediated binding and fusion and the potential application of these liposomes as delivery vehicles for therapeutic agents are discussed.
Shangguan
T
T
The Liposome Company, Inc., Princeton, NJ 08540, USA.
Pak
C C
CC
Ali
S
S
Janoff
A S
AS
Meers
P
P
D002118:Calcium / Q000494:pharmacology*; D002413:Cations, Divalent; D003911:Dextrans; D004910:Erythrocyte Membrane; D005456:Fluorescent Dyes; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry*; D016403:Lymphoma, Large B-Cell, Diffuse; D008274:Magnesium; D008561:Membrane Fusion / Q000502:physiology*; D008856:Microscopy, Fluorescence; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D012235:Rhodamines; D014407:Tumor Cells, Cultured
D002413:Cations, Divalent; D003911:Dextrans; D005456:Fluorescent Dyes; C067661:Fluoro-Ruby; D008081:Liposomes; C110434:N-dodecanoyl-dioleoylphosphatidylethanolamine; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D012235:Rhodamines; D008274:Magnesium; D002118:Calcium